39 results about "Bone marrow fibrosis" patented technology

Disclosed is a substance delivery carrier for an extracellular matrix-producing cell in the bone marrow, which comprises a retinoid. Also disclosed is an agent for treating myelofibrosis by utilizing a substance capable of regulating the activity or proliferation of an extracellular matrix-producing cell in the bone marrow.

In part, the present disclosure relates methods for treating, preventing, or reducing the progression rate and / or severity of myelofibrosis or one or more complications of myelofibrosis (extramedullary hematopoiesis, splenomegaly, anemia, and fibrosis). In certain aspects, the disclosure provides ActRIIB antagonists for use in treating, preventing, or reducing the progression rate and / or severity of one or more complications associated with Janus kinase inhibitor therapy in a patient (e.g., anemia).

The invention relates to clinical application of a substituted aryl hydrazone compound and a derivative thereof serving as an anti-tumor necrosis factor inhibitor. A test result shows that the compound has a lower cytotoxicity in animal bodies, so the medical compound is expected to be used as an anti-TNF-alpha and TNF-beta inhibitor in the clinical application and is mainly used for treating some TNF related immunological diseases such as rheumatic arthritis, inflammatory bowel diseases, diabetes, hematosepsis, psoriasis, ankylosing spondylitis and some communicable diseases including HIV. A current TNF related research also shows that the medical compound can be used for treating clinical blood and solid tumor such as myelodysplastic syndrome, myelofibrosis, acute bone marrow cell leucocythemia, acute / chronic graft-versus-host reaction, ovarian cancer, nephrocyte cancer and the like.

Provided herein are compositions and methods for treating myelofibrosis in a subject. The methods comprise administering to the subject an effective amount of compound which is which is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide or a pharmaceutical salt thereof or a hydrate thereof.

The invention relates to the technical field of medicines, in particular to application of LY3009120 in preparation of a medicine for treating myeloproliferative tumors. The myeloproliferative tumors comprise polycythemia vera, primary thrombocythemia and myelofibrosis, and particularly, the myeloproliferative tumors resistant to rucotinib. When the LY3009120 is used for treating the myeloproliferative tumors, a new treatment way is provided for the majority of patients with the myeloproliferative tumors, and more choices are provided for clinicians and the patients. For a myeloproliferative tumor patient with drug resistance to rucotinib, LY3009120 can provide continuous oral drug treatment for the patient, and bone marrow transplantation is avoided. LY3009120 can be chemically synthesized, and the cost is lower than that of a biological agent. And through a first-stage clinical experiment, the side reaction is less and lighter, and the tolerance of a clinical patient is good.

The invention discloses a JAK kinase inhibitor with 4-amino-(1H)-pyrazole structure and a preparation method and application thereof. The compound has a structure shown in general formula (I) or (II), and the invention provides a specific preparation method of the compound and application of the compound in preventing or treating inflammation, tumor and blood related diseases; the inflammation, tumor and blood related diseases include psoriasis, rheumatic arthritis, polycythemia vera, cicatricial alopecia, primary thrombocythemia, ulcerative colitis, myelofibrosis with myeloid metaplasia, severe combined immune deficiency, various leukemia, various solid tumors and the like.

In part, the disclosure relates to methods of treating fibrotic cancers by administering one or more Serum Amyloid Protein (SAP) agonists. In certain aspects, the method further comprises the conjoint administration of an anti-cancer therapeutic, e.g., a chemotherapeutic agent. In certain aspects, the disclosure relates to methods of treating myelofibrosis by administering an SAP agonist and optionally one or more anti-cancer therapeutic agents.

The invention discloses a circular circRNA-016901 gene related to leukemia and a purpose thereof. Firstly, the existence of the circular circRNA-016901 gene is proved; through detecting a gene expression condition in a whole body radiation patient, the condition that the expression level of the gene is obviously raised is discovered. Marrow stromal cells transfected with an adenovirus vector of the over-expressed circular circRNA-016901 gene are compared with reference marrow stromal cells transfected with an empty vector; the conditions that the expression quantity of TGF-beta protein in the cells transfected with the adenovirus vector is obviously increased, the myelofibrosis is caused and is unfavorable for hematopoietic cell homing, self updating, proliferation and differentiation, and further the transplanting curative effect of the hematopoietic stem cells can be influenced are discovered, so that the circular circRNA-016901 gene and an expression product of the circular circRNA-016901 gene can be used as a marker for predicting the hematopoietic stem cell transplanting curative effect, and can be used as a target gene for preparing leukemia treating medicines and a medicine.

A pyrrolopyrimidine five-membered azacyclic derivative as a novel JAK kinase (Janus kinase) inhibitor, and use thereof in a preparation of a pharmaceutical product for preventing and / or treating an indication related to a JAK kinase function. The pyrrolopyrimidine five-membered azacyclic derivative is an ideal JAK kinase inhibitor with a high potency, and can be used to treat or prevent diseases such as rheumatoid arthritis, polycythemia vera, psoriasis, primary thrombocytosis, myelofibrosis, and the like.

The invention belongs to the technical field of medicine, and relates to application of a prazole compound in preparation of drugs for prevention and treatment of fibrotic diseases. The pantozol compound is pantoprazole, lansoprazole, omeprazole, eprazole, esomeprazole, rabeprazole and other benzimidazole and pyridine substituted sulfoxide compounds or their derivatives. The fibrotic diseases include lung fibrosis, liver fibrosis, kidney fibrosis, heart fibrosis, endometrial fibrosis, eye fibrosis, pancreas fibrosis, spleen fibroplasia, bone marrow fibrosis, skin fibrosis or diseases induced by fibrosis. The prazole compound can be combined with one or more pharmaceutical carriers to form a pharmaceutical composition. The prazole compound or the pharmaceutical composition thereof can be used alone or in combination with other drugs. Moreover, the prazole compound has the advantages of having an obvious curative effect, few side effects and safe use in the treatment of the fibrotic diseases.

In part, the present disclosure relates methods for treating, preventing, or reducing the progression rate and / or severity of myelofibrosis or one or more complications of myelofibrosis (extramedullary hematopoiesis, splenomegaly, anemia, and fibrosis). In certain aspects, the disclosure provides ActRIIB antagonists for use in treating, preventing, or reducing the progression rate and / or severity of one or more complications associated with Janus kinase inhibitor therapy in a patient (e.g., anemia).

The invention discloses a leukemia-relevant circular circRNA-011235 gene and applications of the leukemia-relevant circular circRNA-011235 gene. According to the leukemia-relevant circular circRNA-011235 gene and the applications of the leukemia-relevant circular circRNA-011235 gene, the existence of the circRNA-011235 gene is proved first, through the detection on the expression condition of the gene in a patient under toal body irradiation, the result shows that the expression level of the circRNA-011235 gene is obviously increased. The marrow stroma cell transfected with the adenovirus vector with the overexpression of the circular circRNA-011235 gene is compared with a contrast marrow stroma cell transfected with a blank carrier, the result shows that the expression quantity of TGF-beta protein in the former cell is obviously increased, consequently, myelofibrosis is caused, then homing, self-renewal, proliferation and differentiation of hematopoietic cells are not facilitated, further, the curative effects of hematopoietic stem cell transplantation are influenced, therefore, the circular circRNA-011235 gene and the expression product of the circular circRNA-011235 gene can be taken as markers for predicating the hematopoietic stem cell transplantation curative effects, and can be taken as target genes and medicines for preparing leukemia medicines.

New therapeutic use of Polypodium extract. A new use of Polypodacea genus extracts is described for the treatment of fibrotic pathologies, such as, scleroderma, pulmonary fibrosis, atherosclerosis, bone marrow fibrosis, liver fibrosis, pancreatic fibrosis, kidney fibrosis, cardiac fibrosis, Dupuytrem's disease and, specially, Peyronie's disease; said fibrotic pathologies are produced by an extracellular matriz (ECM) overexpresion, and by a Transforming Growth Factor (TFG-β) overexpression. It is disclosed extracellular matriz inhibition in vitro; and penis tunica albuginea reduction and plaque redution in patients who suffer Peyronie's diseaseas after Polypodium extracts administration. In a preferred mode, Polypodium extracts are obtained from Polypodium leucotomos rhizomes and extraction with a polar solvent.

New therapeutic use of Polypodium extract. A new use of Polypodacea genus extracts is described for the treatment of fibrotic pathologies, such as, scleroderma, pulmonary fibrosis, atherosclerosis, bone marrow fibrosis, liver fibrosis, pancreatic fibrosis, kidney fibrosis, cardiac fibrosis, Dupuytrem's disease and, specially, Peyronie's disease.

Provided herein are compositions and methods for treating myelofibrosis in a subject. The methods comprise administering to the subject an effective amount of compound which is which is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide or a pharmaceutical salt thereof or a hydrate thereof.

Disclosed is a substance delivery carrier for an extracellular-matrix-producing cell in the bone marrow, which comprises a retinoid. Also disclosed is an agent for treating myelofibrosis by utilizing a substance capable of regulating the activity or proliferation of an extracellular-matrix-producing cell in the bone marrow.

The invention discloses a human primary myelofibrosis cell strain as well as a construction method and application thereof. The primary myelofibrosis cell strain is named as human primary myelofibrosis cell strain ZYXY-M2, and was preserved in China Center for Type Culture Collection (Wuhan university, Wuhan, China) on January 20th, 2021 with the preservation number of CCTCC NO:C202145. The human primary myelofibrosis cell strain is obtained by extracting and separating peripheral blood of a clinical primary myelofibrosis patient to obtain mononuclear cells, and performing in-vitro culture and continuous natural passage. The leukemia cell strain JAK2, CALR and MPL is negative in mutation, ASXL1 is positive in mutation, TP53 is positive in mutation, IKZF1 is positive in mutation, IDH1 is positive in mutation, FLT3 is positive in mutation, and TET1 is positive in mutation. The human primary myelofibrosis cell strain has good in-vitro proliferation ability, can be used as a cell material for studying the development mechanism of human primary myelofibrosis and the in-vitro study of individualized treatment, and can be used for screening and evaluating human primary myelofibrosis drugs in vitro and in vivo and guiding clinical medication.

The invention discloses a human primary myelofibrosis cell line and its construction method and application. The primary myelofibrosis cell line is named human primary myelofibrosis cell line ZYXY‑M2, and was deposited in the China Center for Type Culture Collection (Wuhan University, Wuhan, China) on January 20, 2021, with the preservation number CCTCC NO :C202145. The present invention is obtained by extracting and separating mononuclear cells from the peripheral blood of patients with clinical primary myelofibrosis, and culturing them in vitro for continuous natural passage. The leukemia cell line is negative for JAK2, CALR, and MPL mutations, positive for ASXL1 mutations, positive for TP53 mutations, positive for IKZF1 mutations, positive for IDH1 mutations, positive for FLT3 mutations, and positive for TET1 mutations. With good in vitro proliferation ability, it can be used as a cell material for studying the mechanism of human primary myelofibrosis and individualized treatment in vitro. It can also be used for in vivo and in vitro research of drug screening, evaluation, and guidance for human primary myelofibrosis. Clinical medication.

The invention relates to the application of JAK-1 signaling pathway inhibitors in the preparation of drugs for treating brain injury and / or protecting brain nerves. Inhibitors of the JAK‑1 signaling pathway (one of which is Ruxolitinib, a clinical drug approved by the FDA for the treatment of myelofibrosis) exert neuroprotective effects by (but not limited to) inhibiting the process of pyroptosis. Injured patients provide new theoretical and technical means.

Therapeutic methods and pharmaceutical compositions for treating cancer including a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis in a human subject are described. In certain embodiments, the invention includes therapeutic methods of treating a MPN using a MDM2 inhibitor of Formula (I) or Formula (II).

The invention belongs to the technical field of medicine, and relates to the use of vitamin B2 in preparing medicines for treating and preventing fibrosis diseases. The vitamin B2 is vitamin B2 or its medicinal derivatives. The fibrotic diseases include pulmonary fibrosis, liver fibrosis, renal fibrosis, cardiac fibrosis, endometrial fibrosis, eye fibrosis, pancreatic fibrosis, spleen fibroproliferative disease, myelofibrosis disease or fibrosis induced disease. The vitamin B2 can form a pharmaceutical composition with one or more pharmaceutical carriers. Vitamin B2 or its pharmaceutical composition can be used alone or in combination with other drugs. And it has the advantages of significant curative effect, less toxic and side effects and safe use in treating fibrotic diseases.

The invention relates to traditional Chinese medicine decoction for treating qi-blood deficiency and stagnation type myelofibrosis and a preparation method thereof. The traditional Chinese medicine decoction is prepared from, by weight, 5-13 parts of rhizoma cyperi, 10-20 parts of radix stephaniae cepharanthae, 12-25 parts of radix et caulis acanthopanacis senticosi, 2-7 parts of semen citri reticulatae, 6-12 parts of moutan bark, 9-18 parts of rhizoma corydalis decumbentis, 4-10 parts of akebia fruits, 3-9 parts of fructus polygoni orientalis, 6-12 parts of manyinflorescenced sweetvetch roots, 10-18 parts of white paeony roots, 4-12 parts of roots of wedelia urticaefolia (blume) DC., 14-28 parts of radix codonopsis, 7-15 parts of fructus mori, 9-15 parts of arillus longan and 3-9 parts of costus roots. When the traditional Chinese medicine decoction is used for treating qi-blood deficiency and stagnation type myelofibrosis, the effect is remarkable, the traditional Chinese medicine decoction is reasonable in compatibility and unique in composition, all medicinal materials are combined to achieve the effects of reinforcing qi, nourishing blood, promoting blood circulation, removing stasis and the like, and thereby the purposes of treating both manifestation and root causes of qi-blood deficiency and stagnation type myelofibrosis is achieved.

The invention belongs to the technical field of medicines, and relates to a purpose of vitamin B2 to preparation of medicines for preventing and treating fibrosis diseases. The vitamin B2 is vitamin B2 or other medical derivatives. The fibrosis diseases comprise pulmonary fibrosis, liver fibrosis, kidney fibrosis, heart fibrosis, endometrium fibrosis, eye fibrosis, pancreas fibrosis, spleen fiberhyperplasia diseases, bone marrow fibrosis diseases or fibrosis induced diseases. The vitamin B2 and one or various medical carriers can be prepared into a medical composition. The vitamin B2 or the medical composition can be separately used, or can be used with other medicines in a united manner. The vitamin B2 has the advantages of being notable in treatment effects, low in toxic and side effects and safe to use in the respect of treating the fibrosis diseases.

Therapeutic methods and pharmaceutical compositions for treating a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis, are described. In certain embodiments, the invention includes therapeutic methods of treating a MPN using a combination of a compound of Formula (I) or Formula (II) with a therapeutic agent selected from the group consisting of a JAK inhibitor, an IDH inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, an interferon, a PI3K inhibitor, an AKT inhibitor, an mTOR inhibitor, a nucleoside analog, and combinations thereof.

The invention discloses an application of a polypeptide and belongs to the field of biopharmaceuticals. 1. A polypeptide, characterized in that, the structural domain Pro-Arg-Cys-X-Y-Gly-Glu contained in the polypeptide, wherein X is Trp or Tyr; Y is Arg or Cys; and Arg-Gly-Ala- Asp-Arg-Ala; or the sequence after mutating any amino acid in the above domain; can treat various fibrotic diseases and conditions, including pulmonary fibrosis, liver fibrosis, bone marrow fibrosis, renal fibrosis and myocardial fibrosis , skin fibrosis and lung tissue lesions.

The invention discloses a circular circRNA-016901 gene related to leukemia and a purpose thereof. Firstly, the existence of the circular circRNA-016901 gene is proved; through detecting a gene expression condition in a whole body radiation patient, the condition that the expression level of the gene is obviously raised is discovered. Marrow stromal cells transfected with an adenovirus vector of the over-expressed circular circRNA-016901 gene are compared with reference marrow stromal cells transfected with an empty vector; the conditions that the expression quantity of TGF-beta protein in the cells transfected with the adenovirus vector is obviously increased, the myelofibrosis is caused and is unfavorable for hematopoietic cell homing, self updating, proliferation and differentiation, and further the transplanting curative effect of the hematopoietic stem cells can be influenced are discovered, so that the circular circRNA-016901 gene and an expression product of the circular circRNA-016901 gene can be used as a marker for predicting the hematopoietic stem cell transplanting curative effect, and can be used as a target gene for preparing leukemia treating medicines and a medicine.

Provided herein are methods for treating myeloproliferative neoplasm-associated myelofibrosis in a subject, comprising administering to the subject an ActRIIB signaling inhibitor. Also provided hereinare methods for treating myeloproliferative neoplasm-associated myelofibrosis in a subject in need thereof, wherein the method comprises administering to the subject a pharmaceutically effective amount of an ActRIIB signaling inhibitor, and wherein said treating reduces or palliates one or more symptoms of said myeloproliferative neoplasm-associated myelofibrosis in said subject. Also provided herein is a method for treating anemia in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of an ActRIIB signaling inhibitor, wherein the subject has myeloproliferative neoplasm-associated myelofibrosis.

The invention described herein relates to methods for treating a human subject with myelofibrosis or an MPN-related disorder, comprising administering navitoclax to the subject optionally in combination with ruxolitinib.

The invention relates to application of a compound cortex phellodendri liquid liniment in preparation of a medicine for treating myeloproliferative tumors. The compound cortex phellodendri liquid liniment is found to have a good curative effect on myeloproliferative tumors for the first time, experimental verification is carried out on the myeloproliferative tumors, and animal experimental results show that application of the recurrent cortex phellodendri liquid liniment has a remarkable treatment effect on abnormal increase of various lines of cells of myeloproliferative model mice, so the liniment can be used for remarkably reducing abnormal cell rise caused by myeloproliferative tumors, relieving splenomegaly, regulating the hematopoietic function of a blood system and inhibiting the progress of primary thrombocythemia to myelofibrosis.